Researchers identify new molecule to target in pancreatic cancer

Volume 2, Issue 1, 2013

Summary

Researchers decode a molecular pathway that promotes pancreatic tumor growth, revealing new options for improving treatment.

Peter Storz, Ph.D.

Peter Storz, Ph.D.

Researchers at Mayo Clinic Cancer Center in Florida have identified a new target to improve treatment of pancreatic ductal adenocarcinoma, which accounts for more than 95 percent of pancreatic cancer cases. This fast-growing, often lethal cancer is resistant to conventional chemotherapy.

The researchers decoded a molecular pathway that is always switched on, promoting accelerated growth of pancreatic tumors. That discovery revealed ways to disable the pathway, possibly including the use of the drug bortezomib, which is already approved for several human blood cancers. The findings were published in the Jan. 3, 2013, online issue of the journal PLOS ONE.

"Targeting this pathway to decrease the proliferation of cancer cells may represent a new strategy for pancreatic cancer therapy," said the study's senior investigator, Peter Storz, Ph.D., a biochemist and molecular biologist at the Mayo Clinic Cancer Center.

One feature of pancreatic cancer is increased activity of the transcription factor NF-kB, which turns on expression of genes that keeps the cells proliferating and protects them from death. There are two pathways, known as the classical and alternative, by which NF-kB can be activated. The researchers looked at the alternative pathway, one in which NF-kB is activated differently, and that switches on other genes, compared with the classical signaling pathway. Both the classical and alternative pathways are active in pancreatic cancer.

The Mayo Clinic research team discovered that increased activity of the alternative NF-kB pathway results from suppression of tumor necrosis factor receptor-associated factor 2 (TRAF2). Loss of TRAF2 promotes fast growth of pancreatic tumors and correlates with increased aggressiveness.

The researchers tested this discovery in 55 human samples of pancreatic cancer. They found that in 69 percent TRAF2 wasn't functioning properly and that there were higher levels of other molecules participating in the alternative pathway. "A cocktail of drugs that includes chemotherapy, bortezomib and other inhibitors of molecules activated along the pathway may help pancreatic cancer patients," Dr. Storz said. "Of course, this hypothesis requires extensive clinical testing, but our findings offer a new direction to investigate in improving treatment of pancreatic cancer."